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Original Article

A comparison of the effects of ranitidine and omeprazole on volume and pH of gastric contents in elective surgical patients

Gouda, B. B.*; Lydon, A. M.; Badhe, A.*; Shorten, G. D.

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European Journal of Anaesthesiology: April 2004 - Volume 21 - Issue 4 - p 260-264
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Pneumonitis as a result of pulmonary aspiration of gastric contents is associated with a mortality of 5% [1]. In case of aspiration of gastric contents, the risk of lung damage is determined in part by the volume (in excess of 0.4 mL kg−1) [2], and pH (<2.5) [3] of gastric contents. Our hypothesis is that both ranitidine and omeprazole administered by mouth will decrease residual gastric volume and increase gastric content pH in patients undergoing elective surgery. A prospective, randomized, controlled clinical trial was performed to compare the effects of ranitidine (150 mg) orally and omeprazole (60 mg) orally (each administered on the night before surgery and again 2-3 h preoperatively) on pH and volume of gastric contents in female patients undergoing elective surgery.


With institutional ethics approval (Ethics Committee of Jawaharlal Institute of Postgraduate Medical Education) and having obtained written informed consent from each, 87 inpatients undergoing elective gynaecological surgery were studied. Exclusion criteria were gastrointestinal disease, medications known to alter the rate of gastric emptying, or to alter gastric pH or residual gastric volume, obesity (body weight in excess of 120% of ideal), pregnancy, recent (1 month) surgery, and allergy to either ranitidine or omeprazole.

Patients received (a) omeprazole 60 mg orally on the evening prior to surgery and again 2-3 h prior to induction of anaesthesia; (b) ranitidine 150 mg orally on the evening prior to surgery and again between 2 and 3 h prior to induction of anaesthesia or (c) neither omeprazole nor ranitidine, according to random allocation. All patients received oral diazepam 0.2 mg kg−1 orally 2 h preoperatively.

Anaesthesia was induced with intravenous (i.v.) thiopental 3-5 mg kg−1 and maintained using 70% nitrous oxide and isoflurane in oxygen. Endotracheal intubation was facilitated by administration of succinylcholine 1 mg kg−1 i.v. Anticholinergics were not administered prior to aspiration of gastric contents. Next, a size 18-Fr Salem Sump® (Argyle, St. Louis, MO, USA) orogastric tube was inserted. The correct position of the orogastric tube was verified by insufflation of air during auscultation over the epigastrium. The patient was turned from the supine position onto the right and left sides, aspirating the orogastric tube after each change in position, resulting in a total of five aspiration attempts. The volume and pH of the aspirate were recorded. The gastric aspirate pH was measured using Merck pH paper (Acilit®; Merck, Darmstadt, Germany), impregnated with pH-sensitive indicator accurate over the pH range 0-6 [4].

Based on a reduction in the proportion of patients 'at risk' of pneumonitis (a residual gastric content volume >25 mL and pH >2.5) from 32% [5], to 2% in both the ranitidine and omeprazole groups, and applying a binomial 'at risk' or 'not at risk' status to each patient, the standard deviation is 0.34, and the effect size is 0.3, giving a minimum sample size of 20 per group (α = 0.05, β = 0.2). Data were analysed using the Kruskal-Wallis test or Fisher's Exact test as appropriate. Significance was accepted at P < 0.05.


Of 87 recruited patients, surgery was cancelled in two, induction of anaesthesia occurred longer than 3 h after premedication in nine, and one patient was excluded for non-compliance with fasting requirements. The presented data were obtained from the remaining 75 patients. The three groups were similar in terms of age and weight (Table 1).

Table 1:
Comparison of characteristics in patients receiving ranitidine, omeprazole or neither.

Using the Kruskal-Wallis test (Minitab 14®; Minitab Ltd, State College, PA, USA), preoperative gastric volumes were less in the ranitidine (P < 0.001) and omeprazole (P < 0.001) groups than in the control group (Table 2). The pH of the preoperative gastric contents was greater in the ranitidine (P = 0.003) and omeprazole (P < 0.001) groups than in the control group (Table 2). Preoperative gastric volumes were similar in the omeprazole and ranitidine groups (P = 0.259) (Table 2). The pH of the residual gastric content in the omeprazole group (6.5 (range 6-7)) was greater than that in the ranitidine group (5.4 (range 4.5-6.3)) (P = 0.001) (Table 2). Both pH <2.5 and volume >25 mL were present in none of the patients in either the ranitidine or omeprazole groups, compared to 15 of 25 control patients (P < 0.0001) (Table 2). In case of aspiration of gastric contents, when the risk of pneumonitis is defined by either pH <2.5 or volume >25 mL, 19 of 25 control patients were 'at risk', compared to three of 25 patients in the ranitidine and omeprazole groups, respectively (P < 0.0001) (Table 2).

Table 2:
Volume and pH of residual gastric contents in patients receiving omeprazole, ranitidine or neither.


The most important findings of this study are (a) the majority of patients undergoing elective surgery are 'at risk' of pneumonitis in case of pulmonary aspiration of gastric contents; (b) both omeprazole (60 mg) and ranitidine (150 mg) administered preoperatively are possibly effective in reducing the effects of pulmonary aspiration of gastric contents and (c) omeprazole is more effective than ranitidine in increasing the pH of gastric contents before operation.

Pulmonary tissue damage following aspiration is dependent on both the pH and the volume of the aspirated material [3]. It has been suggested that the critical pH of gastric contents in terms of lung damage is <2.5 [3]. However, pneumonitis has followed aspiration of material of pH 3.5 [6]. Animal studies have demonstrated that gastric pH may be more important than volume in determining morbidity associated with pulmonary aspiration of gastric contents [3]. Critical volumes of gastric contents ranging from 0.4 [2] to 0.8 [7] mL kg−1 of pH <2.5 have been postulated. The traditionally accepted critical thresholds for pH (<2.5) and gastric content volume (<0.4 mL kg−1) have been challenged [8,9]. The incidence of pneumonitis resulting from aspiration of gastric contents is 4.7 per 100 000 anaesthetics administered [1].

Blind aspiration of gastric contents through a wide-bore tube can result in an underestimation of residual gastric volume [10]. However, the magnitude of this underestimate is decreased by aspirating with the patient in several different positions, the technique employed in this study. The addition of a dye dilution technique may not increase accuracy in anaesthetized patients [11]. The volume of gastric contents of the control group (30.6 (13.5) mL) is similar to that previously reported in adult elective surgical inpatients [12,13].

The accuracy of the pH measurement techniques used in this study has been questioned [14,15]. However, Levine and colleagues [16] and Haavik and colleagues [5] have demonstrated good correlation between litmus paper and intragastric pH probes and electronic pH meters, respectively.

In our study, either omeprazole (60 mg) or ranitidine (150 mg) was administered to inpatients undergoing elective gynaecological surgery. Omeprazole acts only at the gastric parietal cell, where it inhibits proton pump activity for 16-18 h by causing irreversible H+,K+-ATPase inhibition, thus decreasing the volume of gastric acid secretion [17]. Side-effects of omeprazole are rare, perhaps due to the selectivity of its site of action [17]. Ranitidine acts as a competitive antagonist at the H2 receptor on the parietal cell [18]. A dose of ranitidine 150 mg administered by mouth produces peak blood concentrations in 60-90 min and therapeutic concentrations are maintained for approximately 8 h [19]. The dose and timing of administration of ranitidine used in this study have previously been used both in patients undergoing Caesarean section [20] and general surgical procedures [21]. Serious side-effects of ranitidine are uncommon but include thrombocytopaenia and hepatitis [20]. In spite of in vitro inhibition of cholinesterase [22], no interaction between succinylcholine and ranitidine has been reported in the clinical setting.

Gastric contents comprise ingested solids and liquids, gastric secretion (approximately 50 mL h−1) and swallowed saliva (approximately 1 mL kg−1h−1) [23]. A decrease in pH of duodenal content inhibits gastric antral motility, and acute inhibition of H+ secretion in the stomach by H2 receptor antagonists increases antroduodenal motility. Ranitidine can decrease [24], increase [25] or have no effect [26] on the rate of gastric emptying. Omeprazole decreases the rate of gastric emptying [27,28], postulated to be mediated by inhibiting motilin secretion [28]. Thus, it is likely that the decrease in gastric content volume mediated by both omeprazole and ranitidine is due to inhibition of gastric secretion.

Previous studies of omeprazole on residual gastric pH and volume have yielded conflicting results. A single 80 mg dose administered orally to obstetric patients on the evening prior to elective Caesarean section resulted in six of the 20 patients remaining at risk of pulmonary aspiration of gastric contents [29]. Omeprazole 40 mg, when compared to ranitidine 150 mg (each administered orally on the night prior to surgery and again on the morning of surgery) was more effective at maintaining residual gastric pH >3.5 and residual gastric volume <25 mL [20]. However, omeprazole 40 mg was less effective at maintaining residual gastric pH compared to ranitidine 300 mg (each administered orally on the night prior to surgery and again on the morning of surgery) [30]. Thus, the dose administered is critically important in determining effectiveness of both ranitidine and omeprazole. Multiple doses of omeprazole decrease gastric acid secretion to a greater extent than a single dose [17]. Administration of omeprazole 40 mg orally on the night prior to surgery or 2 h before operation results in a significant proportion (14% and 28%, respectively) of patients remaining at risk [31]. In this study, we administered a greater dose of omeprazole (60 mg), and compared it to ranitidine 150 mg, administering the drugs both on the night prior to, and again on the morning of, surgery. In our study, omeprazole and ranitidine administration resulted in similar gastric volumes, but greater pH of gastric content in the omeprazole group. This is consistent with previous work [20]. Omeprazole 40 mg, when compared to ranitidine 150 mg, administered orally both on the night prior to and on the morning of elective Caesarean section resulted in similar residual gastric volumes, but greater pH of gastric content in the omeprazole group [20]. This may be explained by the greater reduction in gastric acid secretion produced by omeprazole than H2 receptor antagonists such as ranitidine. Omeprazole produces an almost total inhibition of gastric acid secretion by preventing the final common step of hydrogen ion release into the gastric lumen [17]. Ranitidine achieves a lesser 60-70% reduction in gastric acid secretion because it limits only histamine receptor induced acid secretion, and does not prevent acid secretion mediated by muscarinic and gastrin receptor activation [19]. Clinical responses to different doses of omeprazole and ranitidine demonstrate inter-patient variability [32,33].

Our results indicate that preoperative oral administration of omeprazole (60 mg) or ranitidine (150 mg) is effective in decreasing the risk of pneumonitis as a consequence of pulmonary aspiration of gastric contents in inpatients undergoing surgery. Although both agents are effective in decreasing the volume of gastric contents, omeprazole increases the pH of gastric contents to a greater extent than ranitidine. It is emphasized that the consistent beneficial effect of omeprazole was achieved using repeated administration of a relatively large dose (60 mg). In deciding on indications for preoperative administration of omeprazole and ranitidine, clinicians must weigh the costs, risks and efficacy of drug administration against the effects of pneumonitis in the event of pulmonary aspiration of gastric contents.


1. Olsson GL, Hallen B, Hambraeus-Jonzon K. Aspiration during anaesthesia: a computer-aided study of 185 358 anaesthetics. Acta Anaesthesiol Scand 1986; 30: 84-92.
2. Roberts RB, Shirley MA. Reducing the risk of acid aspiration during cesarian section. Anesth Analg 1974; 53: 859-868.
3. James CF, Modell JH, Gibbs CP, Kuck EJ, Ruiz BC. Pulmonary aspiration - effects of volume and pH in the rat. Anesth Analg 1984; 63: 665-668.
4. Chaffe A. Which pH paper? Br J Anaesth 1987; 59: 1189-1191.
5. Haavik PE, Soreide E, Hofstad B, Steen PA. Does preoperative anxiety influence gastric fluid volume and acidity? Anesth Analg 1992; 75: 91-94.
6. Taylor G. Acid pulmonary aspiration syndrome after antacids. A case report. Br J Anaesth 1975; 47: 615-617.
7. Raidoo DM, Rocke DA, Brock-Utne JG, Marszalek A, Engelbrecht HE. Critical volume for pulmonary acid aspiration: reappraisal in a primate model. Br J Anaesth 1990; 65: 248-250.
8. Kallar SK, Everett LL. Potential risks and preventive measures for pulmonary aspiration: new concepts in preoperative fasting guidelines. Anesth Analg 1993; 77: 171-182.
9. Engelhardt T, Webster NR. Pulmonary aspiration of gastric contents in anaesthesia. Br J Anaesth 1999; 83: 453-460.
10. Taylor WJ, Champion MC, Barry AW, Hurtig JB. Measuring gastric contents during general anaesthesia: evaluation of blind gastric aspiration. Can J Anaesth 1989; 36: 51-54.
11. Hardy JF, Plourde G, Lebrun M, Cote C, Dubes S, Lepage Y. Determining gastric contents during general anaesthesia: evaluation of two methods. Can J Anaesth 1987; 34: 474-477.
12. Maltby JR, Sutherland AD, Sale JP, Shaffer EA. Preoperative oral fluids: is a five hour fast justified prior to elective surgery? Anesth Analg 1986; 65: 112-116.
13. Manchikanti I, Colliver JA, Marrero TC, Roush JR. Assessment of age-related acid aspiration risk factors in pediatric, adult and geriatric patients. Anesth Analg 1985; 64: 11-17.
14. Dobkin ED, Valcour A, McCloskey CR, et al. Does pH paper accurately reflect gastric pH? Crit Care Med 1990; 18: 985-988.
15. Driscoll DM, Cioffi Jr WG, Molter NC, McManus WF, Mason Jr AD, Pruitt Jr BA. Intragastric pH monitoring. J Burn Rehab 1993; 14: 517-524.
16. Levine RL, Fromm Jr RE, Mojtahedzadeh M, Baghaie AA, Opekun Jr AR. Equivalance of litmus paper and intragastric pH probes for intragastric pH monitoring in the intensive care unit. Crit Care Med 1994; 22: 945-948.
17. Wilde MI, McTavish D. Omeprazole. An update of its pharmacology and therapeutic use in acid-related disorders. Drugs 1994; 48: 91-132.
18. Manchikanti L, Kraus JW, Edds SP. Cimetidine and related drugs in anesthesia. Anesth Analg 1982; 61: 595-608.
19. Woodings EP, Dixon GT, Harrison C, Carey P, Richards DA. Ranitidine - a new H2 receptor antagonist. Gut 1980; 21: 187-191.
20. Ewart MC, Yau G, Gin T, Kotur CF, Oh TE. A comparison of the effects of omeprazole and ranitidine on gastric secretion in women undergoing elective caesarean section. Anaesthesia 1990; 45: 527-530.
21. Levack ID, Bowie RA, Braid DP, et al. Comparison of the effect of two dose schedules of oral omeprazole with oral ranitidine on gastric aspirate pH and volume in patients undergoing elective surgery. Br J Anaesth 1996; 76: 567-569.
22. Hansen WE, Bertl S. Inhibition of cholinesterases by ranitidine. Lancet 1983; 1: 235.
23. Hocking MP, Vogel SB. Physiology of gastric secretion and motility in normal and postgastrectomy (post vagotomy) states. In: Hocking MP, Vogel SB, eds. Woodward's Postgastrectomy Syndromes, 2nd edn. Philadelphia, USA: WB Saunders, 1991: 29-46.
24. Parkman HP, Urbain JL, Knight LC, et al. Effect of gastric acid suppressants on human gastric motility. Gut 1998; 42: 243-250.
25. Amir I, Anwar N, Baraona E, Lieber CS. Ranitidine increases the bioavailability of imbibed alcohol by accelerating gastric emptying. Life Sci 1996; 58: 511-518.
26. Parikh R, Sweetland J, Forster ER, Bedding AW, Farr SJ, Smith JT. Ranitidine bismuth citrate and ranitidine do not affect gastric emptying of a radio-labelled liquid meal. Br J Clin Pharmacol 1994; 38: 577-580.
27. Benini L, Castellani G, Bardelli E, et al. Omeprazole causes delay in gastric emptying of digestible meals. Dig Dis Sci 1996; 41: 469-474.
28. Rasmussen L, Qvist N, Oster-Jorgensen E, Rehfeld JF, Holst JJ, Pedersen SA. A double-blind placebo-controlled study on the effects of omeprazole on gut hormone secretion and gastric emptying rate. Scand J Gastroenterol 1997; 32: 900-905.
29. Moore J, Flynn RJ, Sampaio M, Wilson CM, Gillon KR. Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia 1989; 44: 559-562.
30. Boulay K, Blanloeil Y, Bourveau M, Geay G, Malinovsky JM. Effects of oral ranitidine, famotidine and omeprazole on gastric volume and pH at induction and recovery from general anaesthesia. Br J Anaesth 1994; 73: 475-478.
31. Bouly A, Nathan N, Feiss P. Comparison of omeprazole with cimetidine for prophylaxis of acid aspiration in elective surgery. Eur J Anaesthesiol 1993; 10: 209-213.
32. Roberts CJ. Clinical pharmacokinetics of ranitidine. Clin Pharmacokinet 1984; 9: 211-221.
33. Richardson P, Hawkey CJ, Stack WA. Pharmacology and rationale for use in gastrointestinal disorders. Drugs 1998; 56: 307-335.


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